Cancer is a term used to describe a group of malignancies that all share the common trait of developing when cells in a part of the body begin to grow out of control. Most cancers form as tumors, but can also manifest in the blood and circulate through other tissues where they grow. Cancer malignancies are most commonly treated with a combination of surgery, chemotherapy, and/or radiation therapy. The type of treatment used to treat a specific cancer depends upon several factors including the type of cancer malignancy and the stage during which it was diagnosed.
Imatinib has the following formula:
and its salts, particularly imatinib mesylate, are one of the more commonly used chemotherapeutic agents for treatment of Philadelphia chromosome positive chronic myeloid leukemia in blast phase, accelerated phase or chronic phase. (Gleevec package insert, Novartis Pharmaceuticals Corporation, July 2004).
Imatinib has been shown to have up to a 16 fold inter-patient variability in trough concentrations and that this variability can impact efficacy. (Picard et. al. Blood 2007: 109; 3496-3499, Larson et al. Blood 2008, 111: 4022-4028, Demetri et. al. J Clin Oncol 2009, 27: 3141-3147)
The preferred salt of imatinib is imatinib mesylate has the formula:

Since efficacy of imatinib is improved at higher trough levels and that the drug exhibits wide intra-patient pharmacokinetic variability monitoring concentrations of this drug in blood and adjusting to target levels would be of value in increasing efficacy and minimizing toxicity. The degree of intra- and inter-individual pharmacokinetic variability of imatinib and its salts has been reported to be 16 fold and is impacted by many factors, including:                Organ function        Genetic regulation        Disease state        Age        Drug-drug interaction        Time of drug ingestion        Compliance        
As a result of this variability, equal doses of the same drug in different individuals can result in dramatically different clinical outcomes. The effectiveness of the same dosage of imatinib or its salts varies significantly based upon individual drug clearance and the ultimate serum drug concentration in the patient. Therapeutic drug management would provide the clinician with insight on patient variation in drug administration. With therapeutic drug management, drug dosages could be individualized to the patient, and the chances of effectively treating the cancer without the unwanted side effects would be much higher.
In addition, therapeutic drug management of imatinib or its salts would serve as an excellent tool to ensure compliance (Henk, et al. Proc ASCO 2006, abst. 6083, Feng, et al. Proc ASCO 2006, abst. 6038) in administering chemotherapy with the actual prescribed dosage and achievement of the effective serum concentration levels. Routine therapeutic drug management of imatinib or its salts would require the availability of simple automated tests adaptable to general laboratory equipment. The use of liquid chromatography (LC)-tandem mass spectroscometry to determine the concentration of imatinib, imatinib salts or their chemotherapeutic metabolites in human blood and plasma has been described (Guetens, J Pharm Biomed Anal., 33(5):879-89 2003; Bakhtiar, J Chromatrography B, 768(2):325-340, 2002; Titier, Ther. Drug. Monit., (27)5:634-640, 2005). A LC method to determine the purity of imatinib, imatinib salts or their chemotherapeutic metabolites (Vivekanand, J Pharm Biomed Anal., 28(6):1183-94, 2002) has also been developed but was not used to determine levels in biological fluids. These methods are labor intensive, use expensive equipment and are not amenable to routine clinical laboratory use. An enzymatic assay for measuring imatinib has been developed set forth in U.S. Pat. No. 7,300,768. However there exists no simple immunoassay for determining the presence or quantifying the amount of imatinib in human biological fluids of patients treated with this chemotherapeutic agent.
As seen from the foregoing, there are no immunoassays for determining the presence and/or quantifying the amount of imatinib or its pharmacologically active salts in human biologically fluids. Routine therapeutic drug management of imatinib and its pharmacologically active salts by immunoassays would provide simple automated tests adapted to standard laboratory equipment. However, in order to provide such immunoassays, antibodies specific to imatinib and its pharmacologically active salts must be produced. The derivatives and immunogen used in this assay must impart through these corresponding antibodies produced specific reactivity to imatinib and its pharmacologically active salts without any substantial cross reactivity to therapeutically active or inactive or pharmacologically active or inactive metabolites of imatinib and their salts. In order to be effective in monitoring drug levels, the antibodies should be specific to imatinib and its pharmacologically active salts and not cross reactive with N-desmethyl imatinib
The active metabolite of imatinib which occurs in samples of patients treated with imatinib and its salts is N-desmethyl imatinib which has the formula:

It is this pharmacologically active metabolite which prevents accurate determination imatinib and its salts by immunoassays of samples of patients treated with imatinib and its salts. Therefore it is long been desired to provide antibodies specific to imatinib and its pharmacologically active salts and not cross reactive with N-desmethyl imatinib